Table 7 – Reactome analysis of the AAE6 interactors selected with the Protein-Pathway method. The pathways with a significant FDR (<0.05) are bolded Pathway name Entities Entities Entities UniProt Entities protein name found p-value FDR number P62877 E3 ubiquitin-protein ligase RBX1 (1) Loss of Function of FBXW7 in 3/6 3.31E-05 0.012 Q969H0-1 F-box/WD repeat-containing protein 7 FBXW7 isoform 1 Cancer and NOTCH1 Signaling Q969H0-4 F-box/WD repeat-containing protein 7 FBXW7 isoform 4 P62877 E3 ubiquitin-protein ligase RBX1 (2) FBXW7 Mutants and NOTCH1 in 3/6 3.31E-05 0.012 Q969H0-1 F-box/WD repeat-containing protein 7 FBXW7 isoform 1 Cancer Q969H0-4 F-box/WD repeat-containing protein 7 FBXW7 isoform 4 P49336 Cyclin-dependent kinase 8 CDK8 P62877 E3 ubiquitin-protein ligase RBX1 (3) NOTCH1 Intracellular Domain 5/48 1.30E-04 0.019 Q969H0-1 F-box/WD repeat-containing protein 7 FBXW7 isoform 1 Regulates Transcription Q969H0-4 F-box/WD repeat-containing protein 7 FBXW7 isoform 4 Q92830 Histone acetyltransferase KAT2A P04637 Cellular tumour antigen P53 (4) Regulation of TP53 Expression 2/2 1.94E-04 0.019 O75626 PR domain zinc finger protein 1 PRDM1 (5) Defective Base Excision Repair Q9UIF7-3 Adenine DNA glycosylase MUTYH isoform 3 2/2 1.94E-04 0.019 Associated with MUTYH Q9UIF7-6 Adenine DNA glycosylase MUTYH isoform 6 Q9H2U2 Inorganic pyrophosphatase 2, mitochondrial IPYR2 (6) Pyrophosphate hydrolysis 2/2 1.94E-04 0.019 Q15181 Inorganic pyrophosphatase IPYR (7) Defective MUTYH substrate Q9UIF7-3 Adenine DNA glycosylase MUTYH isoform 3 2/2 1.94E-04 0.019 processing Q9UIF7-6 Adenine DNA glycosylase MUTYH isoform 6 P42345 Serine/threonine-protein kinase mTOR MTOR Q9UGJ0 5'-AMP-activated protein kinase subunit gamma-2 AAKG2 P04637 Cellular tumour antigen P53 (8) TP53 Regulates Metabolic Genes 6/88 2.70E-04 0.019 P14854 Cytochrome c oxidase subunit 6B1 CX6B1 P10599 Thioredoxin THIO Q9HCJ0 Trinucleotide repeat-containing gene 6C protein TNR6C P49336 Cyclin-dependent kinase 8 CDK8 P62877 E3 ubiquitin-protein ligase RBX1 (9) Constitutive Signaling by 5/59 3.34E-04 0.019 Q969H0-1 F-box/WD repeat-containing protein 7 FBXW7 isoform 1 NOTCH1 HD+PEST Domain Mutants Q969H0-4 F-box/WD repeat-containing protein 7 FBXW7 isoform 4 Q92830 Histone acetyltransferase KAT2A Pathway name Entities Entities Entities UniProt Entities protein name found p-value FDR number P49336 Cyclin-dependent kinase 8 CDK8 P62877 E3 ubiquitin-protein ligase RBX1 (10) Signaling by NOTCH1 HD+PEST 5/59 3.34E-04 0.019 Q969H0-1 F-box/WD repeat-containing protein 7 FBXW7 isoform 1 Domain Mutants in Cancer Q969H0-4 F-box/WD repeat-containing protein 7 FBXW7 isoform 4 Q92830 Histone acetyltransferase KAT2A P49336 Cyclin-dependent kinase 8 CDK8 P62877 E3 ubiquitin-protein ligase RBX1 (11) Signaling by NOTCH1 PEST 5/59 3.34E-04 0.019 Q969H0-1 F-box/WD repeat-containing protein 7 FBXW7 isoform 1 Domain Mutants in Cancer Q969H0-4 F-box/WD repeat-containing protein 7 FBXW7 isoform 4 Q92830 Histone acetyltransferase KAT2A P49336 Cyclin-dependent kinase 8 CDK8 P62877 E3 ubiquitin-protein ligase RBX1 (12) Constitutive Signaling by 5/59 3.34E-04 0.019 Q969H0-1 F-box/WD repeat-containing protein 7 FBXW7 isoform 1 NOTCH1 PEST Domain Mutants Q969H0-4 F-box/WD repeat-containing protein 7 FBXW7 isoform 4 Q92830 Histone acetyltransferase KAT2A P49336 Cyclin-dependent kinase 8 CDK8 P62877 E3 ubiquitin-protein ligase RBX1 (13) Signaling by NOTCH1 in Cancer 5/59 3.34E-04 0.019 Q969H0-1 F-box/WD repeat-containing protein 7 FBXW7 isoform 1 Q969H0-4 F-box/WD repeat-containing protein 7 FBXW7 isoform 4 Q92830 Histone acetyltransferase KAT2A P25054 Adenomatous polyposis coli protein APC Q13237 cGMP-dependent protein kinase 2 KGP2 P09497 Clathrin light chain B CLCB P62877 E3 ubiquitin-protein ligase RBX1 P56545 PC-terminal-binding protein 2 CTBP2 (14) Signaling by WNT 10/299 8.48E-04 0.044 Q9P219 Protein Daple DAPLE Rod cGMP-specific 3',5'-cyclic phosphodiesterase subunit beta P35913 PDE6B Q8N474 Secreted frizzled-related protein 1 SFRP1 O14641 Segment polarity protein dishevelled homolog DVL2 Q9HCJ0 Trinucleotide repeat-containing gene 6C protein TNR6C Pathway name Entities Entities Entities UniProt Entities protein name found p-value FDR number P49336 Cyclin-dependent kinase 8 CDK8 P62877 E3 ubiquitin-protein ligase RBX1 (15) Signaling by NOTCH1 5/74 9.23E-04 0.045 Q969H0-1 F-box/WD repeat-containing protein 7 FBXW7 isoform 1 Q969H0-4 F-box/WD repeat-containing protein 7 FBXW7 isoform 4 Q92830 Histone acetyltransferase KAT2A P04637 Cellular tumour antigen P53 P49336 Cyclin-dependent kinase 8 CDK8 P62877 E3 ubiquitin-protein ligase RBX1 Q969H0-1 F-box/WD repeat-containing protein 7 FBXW7 isoform 1 (16) Signaling by NOTCH 8/205 0.0011 0.049 Q969H0-4 F-box/WD repeat-containing protein 7 FBXW7 isoform 4 Q92830 Histone acetyltransferase KAT2A Q14186 Transcription factor Dp-1 TFDP1 Q9HCJ0 Trinucleotide repeat-containing gene 6C protein TNR6C (17) Negative regulation of TCF- Q9P219 Protein Daple DAPLE dependent signaling by DVL- 2/5 0.0012 0.049 O14641 Segment polarity protein dishevelled homolog DVL2 interacting proteins (18) Activation of NOXA and P04637 Cellular tumour antigen P53 2/5 0.0012 0.049 translocation to mitochondria Q14186 Transcription factor Dp-1 TFDP1 Q9UIF7-3 Adenine DNA glycosylase MUTYH isoform 3 (19) Diseases of Base Excision Repair 2/7 0.0023 0.087 Q9UIF7-6 Adenine DNA glycosylase MUTYH isoform 6 P16870 Carboxypeptidase E CBPE (20) Insulin processing 3/27 0.0026 0.091 Q12840 Kinesin heavy chain isoform 5A KIF5A P33176 Kinesin-1 heavy chain KINH P04637 Cellular tumour antigen P53 P01100 Proto-oncogene c-Fos FOS (21) Oxidative Stress Induced 5/94 0.0026 0.091 P10599 Thioredoxin THIO Senescence Q14186 Transcription factor Dp-1 TFDP1 Q9HCJ0 Trinucleotide repeat-containing gene 6C protein TNR6C P04637 Cellular tumour antigen P53 (22) Pre-NOTCH Transcription and Q92830 Histone acetyltransferase KAT2A 4/62 0.0036 0.113 Translation Q14186 Transcription factor Dp-1 TFDP1 Q9HCJ0 Trinucleotide repeat-containing gene 6C protein TNR6C Pathway name Entities Entities Entities UniProt Entities protein name found p-value FDR number (23) Activation of PUMA and P04637 Cellular tumour antigen P53 2/9 0.0038 0.113 translocation to mitochondria Q14186 Transcription factor Dp-1 TFDP1 Q9UGJ0 5'-AMP-activated protein kinase subunit gamma-2 AAKG2 Q92851 Caspase-10 CASP10 P04637 Cellular tumour antigen p53 P14854 Cytochrome c oxidase subunit 6B1 CX6B1 (24) Transcriptional Regulation by O75626 PR domain zinc finger protein 1 PRDM1 10/367 0.0038 0.113 TP53 P01100 Proto-oncogene c-Fos FOS P42345 Serine/threonine-protein kinase mTOR MTOR P10599 Thioredoxin THIO Q14186 Transcription factor Dp-1 TFDP1 Q9HCJ0 Trinucleotide repeat-containing gene 6C protein TNR6C Q8N139 ATP-binding cassette sub-family A member 6 ABCA6 Q969P5 F-box only protein 32 FBX32 (25) FOXO-mediated transcription 4/66 0.0045 0.124 P23511 Nuclear transcription factor Y subunit alpha NFYA P10599 Thioredoxin THIO Table 8 – Reactome analysis of the EPE6 interactors selected with the Protein-Pathway method Pathway name Entities Entities Entities UniProt Entities protein name found p-value FDR number O14641 Segment polarity protein disheveled homolog DVL-2 (1) Signaling by Hippo 3/20 4.21E-04 0.144 Q9UDY2 Tight junction protein ZO-2 Q9GZV5 WW domain-containing transcription regulator protein 1 WWTR1 Q13509 Tubulin beta-3 chain TUBB3 (2) Post-chaperonin tubulin folding 3/23 6.31E-04 0.144 O75347 Tubulin-specific chaperone A TBCA pathway Q9BTW9 Tubulin-specific chaperone D TBCD (3) Activated NTRK3 signals through P35568 Insulin receptor substrate 1 IRS1 2/6 8.81E-04 0.144 PI3K P27986 Phosphatidylinositol 3-kinase regulatory subunit alpha PIK3R1 Q16533 snRNA-activating protein complex subunit 1 SNAPC1 (4) RNA Polymerase III Transcription 3/28 0.0011 0.144 Q5SXM2 snRNA-activating protein complex subunit 4 SNAPC4 Initiation from Type 3 Promoter A6H8Y1 Transcription factor TFIIIB component B'' homolog BDP1 Q99708 DNA endonuclease RBBP8 (5) HDR through Homologous Q07864 DNA polymerase epsilon catalytic subunit POLE 4/66 0.0013 0.144 Recombination (HRR) P49959 Double strand break repair protein MRE11 P12004 Proliferating cell nuclear antigen PCNA (6) Erythrocytes take up oxygen and P69905 Hemoglobin subunit alpha HBA1 2/8 0.0016 0.144 release carbon dioxide P68871 Hemoglobin subunit beta HBB P35568 Insulin receptor substrate 1 IRS1 (7) PI3K/AKT activation 2/9 0.0020 0.144 P27986 Phosphatidylinositol 3-kinase regulatory subunit alpha PIK3R1 Q16533 snRNA-activating protein complex subunit 1 SNAPC1 (8) RNA Polymerase III Transcription 3/36 0.0023 0.144 Q5SXM2 snRNA-activating protein complex subunit 4 SNAPC4 Initiation A6H8Y1 Transcription factor TFIIIB component B'' homolog BDP1 Q99708 DNA endonuclease RBBP8 (9) HDR through MMEJ (alt-NHEJ) 2/10 0.0024 0.144 P49959 Double strand break repair protein MRE11 Q8N307 Mucin-20 MUC20 P27986 Phosphatidylinositol 3-kinase regulatory subunit alpha PIK3R1 (10) Signaling by MET 4/80 0.0027 0.144 Q6VN20 Ran-binding protein 10 RANBP10 Q96B97 SH3 domain-containing kinase-binding protein 1 SH3KBP1 Pathway name Entities Entities Entities UniProt Entities protein name found p-value FDR number O95786 Antiviral innate immune response receptor RIG-I DDX58 P07550 Beta-2 adrenergic receptor ADRB2 P04637 Cellular tumour antigen p53 Q8IWV2 Contactin-4 CNTN4 Q13618 Cullin-3 CUL3 Q13217 DnaJ homolog subfamily C member 3 DNAJC3 Q9Y297 F-box/WD repeat-containing protein 1A BTRC P02671 Fibrinogen alpha chain FGA Q92696 Geranylgeranyl transferase